NM_001088.3:c.468C>T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001088.3(AANAT):​c.468C>T​(p.Ala156Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,604,098 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 38 hom. )

Consequence

AANAT
NM_001088.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.04
Variant links:
Genes affected
AANAT (HGNC:19): (aralkylamine N-acetyltransferase) The protein encoded by this gene belongs to the acetyltransferase superfamily. It is the penultimate enzyme in melatonin synthesis and controls the night/day rhythm in melatonin production in the vertebrate pineal gland. Melatonin is essential for the function of the circadian clock that influences activity and sleep. This enzyme is regulated by cAMP-dependent phosphorylation that promotes its interaction with 14-3-3 proteins and thus protects the enzyme against proteasomal degradation. This gene may contribute to numerous genetic diseases such as delayed sleep phase syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 17-76469814-C-T is Benign according to our data. Variant chr17-76469814-C-T is described in ClinVar as [Benign]. Clinvar id is 714416.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.04 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00181 (2632/1451750) while in subpopulation EAS AF= 0.0305 (1198/39244). AF 95% confidence interval is 0.0291. There are 38 homozygotes in gnomad4_exome. There are 1299 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AANATNM_001088.3 linkc.468C>T p.Ala156Ala synonymous_variant Exon 4 of 4 ENST00000392492.8 NP_001079.1 Q16613-1F1T0I5
AANATNM_001166579.2 linkc.603C>T p.Ala201Ala synonymous_variant Exon 7 of 7 NP_001160051.1 Q16613-2
AANATNR_110548.2 linkn.724C>T non_coding_transcript_exon_variant Exon 4 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AANATENST00000392492.8 linkc.468C>T p.Ala156Ala synonymous_variant Exon 4 of 4 1 NM_001088.3 ENSP00000376282.2 Q16613-1
AANATENST00000250615.7 linkc.603C>T p.Ala201Ala synonymous_variant Exon 7 of 7 1 ENSP00000250615.2 Q16613-2
AANATENST00000587798.1 linkn.*245C>T non_coding_transcript_exon_variant Exon 4 of 4 5 ENSP00000468239.1 K7ERF6
AANATENST00000587798.1 linkn.*245C>T 3_prime_UTR_variant Exon 4 of 4 5 ENSP00000468239.1 K7ERF6

Frequencies

GnomAD3 genomes
AF:
0.00221
AC:
336
AN:
152230
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.0173
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.0175
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000617
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00326
AC:
748
AN:
229192
Hom.:
14
AF XY:
0.00305
AC XY:
383
AN XY:
125410
show subpopulations
Gnomad AFR exome
AF:
0.0000720
Gnomad AMR exome
AF:
0.0000303
Gnomad ASJ exome
AF:
0.000420
Gnomad EAS exome
AF:
0.0165
Gnomad SAS exome
AF:
0.000486
Gnomad FIN exome
AF:
0.0176
Gnomad NFE exome
AF:
0.000853
Gnomad OTH exome
AF:
0.00372
GnomAD4 exome
AF:
0.00181
AC:
2632
AN:
1451750
Hom.:
38
Cov.:
31
AF XY:
0.00180
AC XY:
1299
AN XY:
721430
show subpopulations
Gnomad4 AFR exome
AF:
0.0000901
Gnomad4 AMR exome
AF:
0.0000229
Gnomad4 ASJ exome
AF:
0.000387
Gnomad4 EAS exome
AF:
0.0305
Gnomad4 SAS exome
AF:
0.000791
Gnomad4 FIN exome
AF:
0.0189
Gnomad4 NFE exome
AF:
0.000236
Gnomad4 OTH exome
AF:
0.00202
GnomAD4 genome
AF:
0.00221
AC:
337
AN:
152348
Hom.:
2
Cov.:
32
AF XY:
0.00303
AC XY:
226
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.0175
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.0175
Gnomad4 NFE
AF:
0.000617
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00109
Hom.:
0
Bravo
AF:
0.000778
Asia WGS
AF:
0.0120
AC:
41
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Mar 29, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.34
DANN
Benign
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2071031; hg19: chr17-74465896; API